In 2006 more than 8,000 adults and children in North America donated either bone marrow (BM) or peripheral blood stem cells (PBSC) for hematopoietic stem cell (HSC) transplantation. Most of these donations came from relatives of the recipient (5000/yr), facilitated by transplant centers caring for that recipient. The remaining donations came from anonymous unrelated adult volunteers, coordinated and carefully regulated by the National Marrow Donor Program (NMDP). Over the past two decades, high quality studies run through the NMDP have resulted in a wealth of data regarding medical and psychological toxicities associated with unrelated HSC donation. Conversely, prospective, quantifiable, and readily comparable data regarding the medical and psychological safety of related donors (RDs) is either outdated or lacking, especially in the potentially vulnerable populations of pediatric and older donors (>60yrs). Our proposed study (called RDSafe, related donor safety study) fills this critical data gap by comparing medical and psychological toxicities of related HSC donors with unrelated donors (UDs) using sophisticated and comprehensive data tools developed by the NMDP. Acute toxicities will be reported using standard scales for common (Modified CTC criteria) and uncommon events. Well-validated, standardized health related quality of life (HRQoL) instruments (SF-36 for adults and PedsQL 4.0 for children) will be used to assess donors and comparisons will be made with age- matched normals and related versus unrelated donors. The study has been developed by members of the Donor Health and Safety Working Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR): the PI of this proposal is a current Co-Chair of this committee. The donor safety experience and data tools of the NMDP will be combined with statistical expertise provided by the Resource for Clinical Investigations in Blood and Marrow Transplant (RCI-BMT) of the CIBMTR. The study has been designed to enhance accrual of pediatric and older RDs, in order to gather sufficient data to provide toxicity risk profiles specific to these groups. Forty CIBMTR transplant centers and over 80 pediatric transplant centers from the Children's Oncology Group have committed to enroll RDs. This cohort will be compared to a concurrently enrolled cohort of UDs collected at over 70 NMDP donor centers. Among other significant contributions, the information gathered from the RDSafe study will 1) define differences in the medical and psychological outcomes of RDs vs. UDs and compare them with age-matched normals, 2) segment the RD population into categories of lower and higher risk, identifying vulnerable populations of donors, 3) describe differences in risk of BM vs. PBSC donation in RD of all ages, 4) define standards for informed consent of RD, and 5) identify donors who are at medical or psychological risk to be significantly harmed by donation.